Drosophila Unc-13 is essential for synaptic transmission

The UNC-13 protein family has been suggested to be critical for synaptic ve sicle dynamics based on its interactions with Syntaxin, Munc-18 and Doc 2 a lpha. We cloned the Drosophila homolog (Dunc-13) and characterized its func tion using a combination of electrophysiology and ultrastructural analyses. Dunc-13 contained a C1 lipid-binding motif and two C2 calcium-binding doma ins, and its expression was restricted to neurons. Elimination of dune-13 e xpression abolished synaptic transmission, an effect comparable only to rem oval of the core complex proteins Syntaxin and Synaptobrevin. Transmitter r elease remained impaired under elevated calcium influx or application of hy perosmotic saline. Ultrastructurally, mutant terminals accumulated docked v esicles at presynaptic release sites. We conclude that Dunc-13 is essential for a stage of neurotransmission following vesicle docking and before fusi on.